TY - JOUR T1 - Impaired Therapeutic Efficacy of Bone Marrow Cells from Post-Myocardial Infarction Patients in the TIME and LateTIME Clinical Trials JF - bioRxiv DO - 10.1101/721860 SP - 721860 AU - Xiaoyin Wang AU - Ronak Derakhshandeh AU - Hilda J. Rodriguez AU - Daniel D. Han AU - Dmitry S. Kostyushev AU - Timothy D. Henry AU - Jay H. Traverse AU - Lem Moyé AU - Robert D. Simari AU - Doris A. Taylor AU - Matthew L. Springer Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/08/01/721860.abstract N2 - Implantation of bone marrow-derived cells (BMCs) into mouse hearts post-myocardial infarction (MI) limits cardiac functional decline. However, clinical trials of post-MI BMC therapy have yielded conflicting results. While most laboratory experiments use healthy BMC donor mice, clinical trials use post-MI autologous BMCs. Post-MI mouse BMCs are therapeutically impaired, due to inflammatory changes in BMC composition. Thus, therapeutic efficacy of the BMCs progressively worsens after MI but recovers as donor inflammatory response resolves. The availability of post-MI patient BM mononuclear cells (MNCs) from the TIME and LateTIME clinical trials enabled us to test if human post-MI MNCs undergo a similar period of impaired efficacy. We hypothesized that MNCs from TIME trial patients would be less therapeutic than healthy human donor MNCs when implanted into post-MI mouse hearts, and that therapeutic properties would be restored in MNCs from LateTIME trial patients. Post-MI SCID mice received MNCs from healthy donors, TIME patients, or LateTIME patients. Cardiac function improved considerably in the healthy donor group, but neither the TIME nor LateTIME group showed therapeutic effect. Conclusion: post-MI human MNCs lack therapeutic benefits possessed by healthy MNCs, which may partially explain why BMC clinical trials have been less successful than mouse studies. ER -